Reduction of plasma membrane glutamate transport potentiates insulin but not glucagon secretion in pancreatic islet cells

Autor: Asllan Gjinovci, Jorge Tamarit-Rodriguez, Andreas Wiederkehr, Nicole Feldmann, Claes B. Wollheim, Rafael Martín del Río
Rok vydání: 2011
Předmět:
Male
Gamma-Aminobutyric Acid/metabolism
Pyrrolidines
Transcription
Genetic
Glutamine
Insulin-Secreting Cells/metabolism/secretion
Malates
Biochemistry
Endocrinology
Insulin-Secreting Cells
Insulin Secretion
Insulin
Dicarboxylic Acids
Glucagon-Secreting Cells/metabolism/secretion
Malates/metabolism
Cells
Cultured
gamma-Aminobutyric Acid
Alanine/metabolism
Alanine
biology
Glucagon/metabolism/secretion
Glutamate receptor
Glucagon secretion
Cell Membrane/metabolism/secretion
Glutamic Acid/metabolism/secretion
Epinephrine/pharmacology
Glutamine/metabolism
medicine.anatomical_structure
Glutamate dehydrogenase 1
Insulin/metabolism/secretion
Ketoglutaric Acids
medicine.medical_specialty
Epinephrine
Dicarboxylic Acids/pharmacology
Glutamate Plasma Membrane Transport Proteins/antagonists & inhibitors/genetics/metabolism
Glutamic Acid
Glutamate Plasma Membrane Transport Proteins
Glucagon
Internal medicine
medicine
Animals
Secretion
Rats
Wistar
ddc:612
Molecular Biology
Ketoglutaric Acids/metabolism
Aspartic Acid
Pancreatic islets
Pyrrolidines/pharmacology
Cell Membrane
Glutamic acid
Rats
Glucose
Glucagon-Secreting Cells
biology.protein
Glucose/metabolism/pharmacology
Aspartic Acid/metabolism
Zdroj: Molecular and Cellular Endocrinology, Vol. 338, No 1-2 (2011) pp. 46-57
ISSN: 1872-8057
0303-7207
Popis: Glutamate is generated during nutrient stimulation of pancreatic islets and has been proposed to act both as an intra- and extra-cellular messenger molecule. We demonstrate that glutamate is not co-secreted with the hormones from intact islets or purified α- and β-cells. Fractional glutamate release was 5-50 times higher than hormone secretion. Furthermore, various hormone secretagogues did not elicit glutamate efflux. Interestingly, epinephrine even decreased glutamate release while increasing glucagon secretion. Rather than being co-secreted with hormones, we show that glutamate is mainly released via plasma membrane excitatory amino acid transporters (EAAT) by uptake reversal. Transcripts for EAAT1, 2 and 3 were present in both rat α- and β-cells. Inhibition of EAATs by L-trans-pyrrolidine-2,4-dicarboxylate augmented intra-cellular glutamate and α-ketoglutarate contents and potentiated glucose-stimulated insulin secretion from islets and purified β-cells without affecting glucagon secretion from α-cells. In conclusion, intra-cellular glutamate-derived metabolite pools are linked to glucose-stimulated insulin but not glucagon secretion.
Databáze: OpenAIRE
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